Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells
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TLDR
Pancreatic β cells are sensitive to excessive endoplasmic reticulum stress and dysregulated eIF2α phosphorylation, as indicated by transcriptome data, monogenic forms of diabetes and pharmacological studies, and should be taken into consideration when devising new therapeutic approaches for diabetes.Abstract:
Background
Pancreatic β cell dysfunction and death are central in the pathogenesis of most if not all forms of diabetes. Understanding the molecular mechanisms underlying β cell failure is important to develop β cell protective approaches.read more
Citations
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Pancreatic β-cells in type 1 and type 2 diabetes mellitus: different pathways to failure.
TL;DR: New findings from studies performed on human β-cells or on samples obtained from patients with type 1 or type 2 diabetes mellitus are highlighted, focusing on studies performed at the β-cell level and the identification and characterization of the role of T1DM and T2DM candidate genes at theβ-celllevel.
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Recent Insights Into Mechanisms of β-Cell Lipo- and Glucolipotoxicity in Type 2 Diabetes.
TL;DR: The current evidence supporting the role of pancreatic β-cell lipo- and glucolipotoxicity in type 2 diabetes is reviewed, including lipid-based interventions in humans, prospective epidemiological studies and human genetic findings.
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Insulin mutations impair beta-cell development in a patient-derived iPSC model of neonatal diabetes
Diego Balboa,Jonna Saarimäki-Vire,Daniel Borshagovski,Mantas Survila,Päivi Lindholm,Emilia Galli,Solja Eurola,Jarkko Ustinov,Heli Grym,Hanna Huopio,Juha Partanen,Kirmo Wartiovaara,Kirmo Wartiovaara,Timo Otonkoski +13 more
TL;DR: It is shown that misfolded proinsulin impairs developingBeta-cell proliferation without increasing apoptosis, and neonatal diabetes-associated INS-mutations lead to defective beta-cell mass expansion, contributing to diabetes development.
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Regulation of autophagy by canonical and non-canonical ER stress responses.
TL;DR: Recent findings on the molecular mechanisms by which canonical and non-canonical ER stress responses can activate cytoprotective autophagy and contribute to tumor growth and therapy resistance are reviewed.
Calcium release channel RyR2 regulates insulin release and glucose homeostasis
Gaetano Santulli,Gennaro Pagano,Gennaro Pagano,Gennaro Pagano,Celestino Sardu,Celestino Sardu,Celestino Sardu,Wenjun Xie,Steven Reiken,Salvatore Luca D'Ascia,Michele Cannone,Nicola Marziliano,Bruno Trimarco,Theresa A. Guise,Alain Lacampagne,Andrew R. Marks +15 more
TL;DR: It is discovered that CPVT patients with mutant leaky RyR2 present with glucose intolerance, which was heretofore unappreciated, and the effects of the pharmacological inhibition of intracellular Ca2+ leak are verified.
References
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Association Studies of Genetic Variation in the WFS1 Gene and Type 2 Diabetes in U.K. Populations
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TL;DR: The results provide the first evidence that variation in the WFS1 gene may influence susceptibility to type 2 diabetes.